Using two different cell-mediated typing assays (secondary lymphocyte proliferative responses and secondary cell-mediated cytotoxicity) we have defined five new HLA-linked antigens designated "SB antigens" (secondary B cell). A reliable system of primed lymphocyte typing for these antigens has been perfected using frozen reagents, and a statistical algorithm for scoring the results is used. Genetic studies suggest that the SB antigens are encoded by a single HLA-linked gene. These antigens have striking similarities to the DR antigens with respect to genetics, tissue distribution and function. However, studies of recombinant families and of mutant cell lines demonstrate that the SB antigens are encoded by a gene distinct from DR, which maps between HLA-DR and GLO. The discovery of this new gene in our laboratory has prompted a large number of collaborations, both to utilize the expertise of other laboratories, and to help others learn to define the SB gene products.